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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-01933 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| RAD2156-11 | Other Identifier | Winship Cancer Institute | |
| P30CA138292 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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This phase I trial studies the side effects and best dose of hypofractionated radiosurgery in treating patients with large brain metastasis. Stereotactic radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue. Giving fractionated stereotactic radiosurgery may kill more tumor cells.
PRIMARY OBJECTIVE:
To demonstrate the safety and feasibility of treating brain metastases or resection cavities greater than 3 cm with hypofractionated radiosurgery and to determine the maximum-tolerated radiation dose for hypofractionated radiosurgery (HR) delivered in 5 fractions, 2-3 fractions per week.
OUTLINE: This is a dose-escalation study.
Patients undergo hypofractionated stereotactic radiosurgery 2-3 times weekly (5 fractions total) for 2-3 weeks.
After completion of study treatment, patients are followed up at 1 month and then every 3 months thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hypofractionated Radiosurgery | Experimental | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hypofractionated Radiosurgery | Radiation | Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Hypofractionated Radiosurgery Defined as the Highest Dose Level Where a Grade 3 or Greater With an Attribution Score of ≥ 3 Develops in ≤ 2 of 6 Patients in a Dose Group | Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The rate of toxicities will be calculated with 95% confidence interval (CI). | 4 months |
| Percentage of Participants With Neurologic Toxicity/Radiation Necrosis Possibly Due to Treatment, Graded According to the CTCAE Version 4.03 as Grade 2 or Greater. | Number | Up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Local Control; Lack of Progression of Disease in Resection Cavity as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria | Cumulative incidences of local brain progression will be calculated by Kaplan-Meier method with 95% CI. | 24 months |
| Intercranial Progression Free Survival: Lack of Progression of Disease in Surrounding Brain as Defined by RECIST Criteria |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bree Eaton, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia | 30322 | United States | ||
| Emory Saint Joseph's Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | Hypofractionated Radiosurgery - 6 Gy x 5 Level 0 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. |
| FG001 | Hypofractionated Radiosurgery - 6.5 Gy x 5 Level 1 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. |
| FG002 | Hypofractionated Radiosurgery -7 Gy x 5 Level 2 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Hypofractionated Radiosurgery- 6 Gy x 5 Level 0 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) of Hypofractionated Radiosurgery Defined as the Highest Dose Level Where a Grade 3 or Greater With an Attribution Score of ≥ 3 Develops in ≤ 2 of 6 Patients in a Dose Group | Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The rate of toxicities will be calculated with 95% confidence interval (CI). | Posted | Number | Gy x 5 fractions | 4 months |
|
24 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Hypofractionated Radiosurgery - 6 Gy x 5 Level 0 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intracranial Hemorrhage | Nervous system disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bree Eaton, MD | Emory University | 404-727-5658 | brupper@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 15, 2020 | Dec 2, 2024 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 1, 2020 | Apr 28, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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Percentage of patients with distant brain progression at the defined time point, with each individual patient's time to progression calculated by Kaplan-Meier method with 95% CI. |
| 12 months |
| Freedom From Failure/Progression Free Survival | Up to 2 years |
| Overall Survival (OS): Death From Any Cause | The median of OS time with 95% CI will be calculated by Kaplan-Meier method. | Up to 2 years |
| Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Scores | Percentage of Participants with a Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Z-Score of ≤ -1. | Up to 4 months |
| Quality of Life (QOL) Outcomes: Using the Quality of Life Questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br). | Patients completed the FACT-BR at baseline and in follow-up. Responses are summed at each encounter to create a score. Total assessments combine scores range from 0-200. The higher the score, the better the QOL. Change from baseline to 4-month follow-up was calculated. A notable change is defined 20 point or greater increase or decrease in total score from baseline to 4-month follow-up score. | Up to 2 years |
| Atlanta |
| Georgia |
| 30342 |
| United States |
| BG001 | Hypofractionated Radiosurgery- 6.5 Gy x 5 Level 1 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. |
| BG002 | Hypofractionated Radiosurgery-7 Gy x 5 Level 2 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Percentage of Participants With Neurologic Toxicity/Radiation Necrosis Possibly Due to Treatment, Graded According to the CTCAE Version 4.03 as Grade 2 or Greater. | Number | Posted | Number | percentage of participants | Up to 2 years |
|
|
|
| Secondary | Local Control; Lack of Progression of Disease in Resection Cavity as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria | Cumulative incidences of local brain progression will be calculated by Kaplan-Meier method with 95% CI. | Pre-specified that data would be combined in the protocol. Pre-specified that data would be combined in the protocol because the study was designed to test safety (reported per dose level), but it was not hypothesized, designed or powered to support comparisons of efficacy outcomes between dose levels. | Posted | Number | 95% Confidence Interval | Percentage of participants | 24 months |
|
|
|
| Secondary | Intercranial Progression Free Survival: Lack of Progression of Disease in Surrounding Brain as Defined by RECIST Criteria | Percentage of patients with distant brain progression at the defined time point, with each individual patient's time to progression calculated by Kaplan-Meier method with 95% CI. | Pre-specified that data would be combined in the protocol. Pre-specified that data would be combined in the protocol because the study was designed to test safety (reported per dose level), but it was not hypothesized, designed or powered to support comparisons of efficacy outcomes between dose levels. | Posted | Number | 95% Confidence Interval | Percentage of participants | 12 months |
|
|
|
| Secondary | Freedom From Failure/Progression Free Survival | Pre-specified that data would be combined in the protocol. Pre-specified that data would be combined in the protocol because the study was designed to test safety (reported per dose level), but it was not hypothesized, designed or powered to support comparisons of efficacy outcomes between dose levels. | Posted | Median | 95% Confidence Interval | Months | Up to 2 years |
|
|
|
| Secondary | Overall Survival (OS): Death From Any Cause | The median of OS time with 95% CI will be calculated by Kaplan-Meier method. | Pre-specified that data would be combined in the protocol. Pre-specified that data would be combined in the protocol because the study was designed to test safety (reported per dose level), but it was not hypothesized, designed or powered to support comparisons of efficacy outcomes between dose levels. | Posted | Median | 95% Confidence Interval | months | Up to 2 years |
|
|
|
| Secondary | Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Scores | Percentage of Participants with a Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Z-Score of ≤ -1. | Pre-specified that data would be combined in the protocol. Pre-specified that data would be combined in the protocol because the study was designed to test safety (reported per dose level), but it was not hypothesized, designed or powered to support comparisons of efficacy outcomes between dose levels. | Posted | Number | Percentage of participants | Up to 4 months |
|
|
|
| Secondary | Quality of Life (QOL) Outcomes: Using the Quality of Life Questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br). | Patients completed the FACT-BR at baseline and in follow-up. Responses are summed at each encounter to create a score. Total assessments combine scores range from 0-200. The higher the score, the better the QOL. Change from baseline to 4-month follow-up was calculated. A notable change is defined 20 point or greater increase or decrease in total score from baseline to 4-month follow-up score. | Pre-specified that data would be combined in the protocol. Pre-specified that data would be combined in the protocol because the study was designed to test safety (reported per dose level), but it was not hypothesized, designed or powered to support comparisons of efficacy outcomes between dose levels. | Posted | Number | participants | Up to 2 years |
|
|
|
| 3 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | Hypofractionated Radiosurgery - 6.5 Gy x 5 Level 1 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. | 6 | 12 | 0 | 12 | 12 | 12 |
| EG002 | Hypofractionated Radiosurgery -7 Gy x 5 Level 2 | HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. Hypofractionated Radiosurgery: Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week. | 6 | 9 | 3 | 9 | 9 | 9 |
| Seizure | Nervous system disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Radiation Necrosis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Seizure | Nervous system disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Motor Weakness | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Aphasia | Nervous system disorders | Non-systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Cognitive Disturbance | Nervous system disorders | Non-systematic Assessment |
|
| Visual Disturbance | Eye disorders | Non-systematic Assessment |
|
| Imbalance | Nervous system disorders | Non-systematic Assessment |
|
| Mood Alteration | Psychiatric disorders | Non-systematic Assessment |
|
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| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |